비타민K2 (동맥 석회화)

Effects of One-Year Menaquinone-7 Supplementation on Vascular Stiffness and Blood Pressure in Post-Menopausal Women.

1. Nutrients. 2025 Feb 27;17(5):815. doi: 10.3390/nu17050815. Effects of One-Year Menaquinone-7 Supplementation on Vascular Stiffness and Blood Pressure in Post-Menopausal Women. de Vries F(1), Bittner R(1)(2), Maresz K(3), Machuron F(4), Gåserød O(2), Jeanne JF(5), Schurgers LJ(1)(6). Author i

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

2. Nephrol Dial Transplant. 2023 Feb 28;38(3):746-756. doi: 10.1093/ndt/gfac191. Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial. Holden RM(1)(2), Booth SL(3), Zimmerman

Warfarin induces cardiovascular damage in mice.

3. Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2618-24. doi: 10.1161/ATVBAHA.113.302244. Epub 2013 Aug 29. Warfarin induces cardiovascular damage in mice. Krüger T(1), Oelenberg S, Kaesler N, Schurgers LJ, van de Sandt AM, Boor P, Schlieper G, Brandenburg VM, Fekete BC, Veulemans V, Ketteler

Treatment with vitamin k(2) combined with bisphosphonates synergistically inhibits calcification in cultured smooth muscle cells.

4. J Atheroscler Thromb. 2007 Dec;14(6):317-24. doi: 10.5551/jat.e501. Epub 2007 Dec 17. Treatment with vitamin k(2) combined with bisphosphonates synergistically inhibits calcification in cultured smooth muscle cells. Saito E(1), Wachi H, Sato F, Sugitani H, Seyama Y. Author information: (1)De

Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials.

5. Nutrients. 2020 Sep 23;12(10):2909. doi: 10.3390/nu12102909. Vitamin K Supplementation for the Prevention of Cardiovascular Disease: Where Is the Evidence? A Systematic Review of Controlled Trials. Vlasschaert C(1), Goss CJ(1), Pilkey NG(1), McKeown S(2), Holden RM(1)(3). Author information:

Vitamin K for the primary prevention of cardiovascular disease.

6. Cochrane Database Syst Rev. 2015 Sep 21;2015(9):CD011148. doi: 10.1002/14651858.CD011148.pub2. Vitamin K for the primary prevention of cardiovascular disease. Hartley L(1), Clar C, Ghannam O, Flowers N, Stranges S, Rees K. Author information: (1)Division of Health Sciences, Warwick Medical Sc

The Effects of Vitamin K2 on Recovery from Muscle-Damaging Resistance Exercise in Young and Older Adults: The TAKEOVER Randomized Controlled Trial.

1. Med Sci Sports Exerc. 2026 Apr 1;58(4):683-694. doi: 10.1249/MSS.0000000000003901. Epub 2026 Mar 5. The Effects of Vitamin K2 on Recovery from Muscle-Damaging Resistance Exercise in Young and Older Adults: The TAKEOVER Randomized Controlled Trial. Lithgow H(1)(2), Johnston L(3), Ho F(4), Dunning E(1), Nakada S(4), Celis-Morales C(1)(5)(6), Hunter AM(7)(8)(9), Lees JS(1), Mark PB(1), Quinn TJ(1), Gray SR(1)(10). Author information: (1)School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UNITED KINGDOM. (2)School of School of Energy, Geoscience, Infrastructure and Society, Heriot-Watt University, Edinburgh, UNITED KINGDOM. (3)School of Life Sciences, University of Glasgow, Glasgow, UNITED KINGDOM. (4)School of Health and Wellbeing, University of Glasgow, Glasgow, UNITED KINGDOM. (5)Human Performance Lab, Education, Physical Activity, and Health Research Unit, Universidad Católica del Maule, Talca, CHILE. (6)High-Altitude Medicine Research Centre (CEIMA), Universidad Arturo Prat, Iquique, CHILE. (7)Department of Sports Science, Nottingham Trent University, Nottingham, UNITED KINGDOM. (8)School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Aberdeen, UNITED KINGDOM. (9)Faculty of Health Sciences and Sport, University of Stirling, Stirling, UNITED KINGDOM. (10)Institute of Sports Science and Innovation, Lithuanian Sports University, Kaunus, LITHUANIA. PURPOSE: Vitamin K2 supplementation has emerged as a strategy to enhance recovery and modulate postexercise physiological responses. This study aimed to assess the effects of vitamin K2 on recovery from muscle-damaging exercise in young and older adults. METHODS: Healthy young (18-40 yr) and older (65+ yr) adults were randomly assigned to either vitamin K2 (menaquinone-7, MK-7, 240 μg/d) or placebo (cellulose) for 12 wk in this double-blind randomized controlled trial. Before and after supplementation, knee extensor maximal torque, functional ability, muscle soreness, and systemic blood markers of muscle damage and inflammation were measured before (0 h) and 3, 24, 48, and 72-h postexercise. Data were analyzed using regression and mixed models. RESULTS: Seventy-one participants (35 young and 36 older) completed the study, with 12 wk of vitamin K2 supplementation increasing circulating MK-7 levels (P-value <0.001). There were no supplement × time effects for any variables. Significant supplement × time × older age interaction effects were noted for electromechanical delay (EMD) (P-value = 0.03), electromyography root mean square (RMS) (P-value = 0.01), interleukin-6 (IL-6) concentrations (P-value <0.001), and creatine kinase (CK) levels (P-value = 0.02). In older adults, after 12 wk, EMD appeared lower at all time points and RMS higher postexercise in the vitamin K2 group. No clear pattern in IL-6 or CK was observed, but at 72-h postexercise CK was lower in older adults in the vitamin K2 group. CONCLUSIONS: Vitamin K2 supplementation had no effect on muscle strength, physical function, muscle soreness, or inflammatory responses in the recovery period after a bout of resistance exercise. Effects of supplementation were observed on EMD, RMS, IL-6, and CK by age and warrant further investigation. Copyright © 2025 by the American College of Sports Medicine. DOI: 10.1249/MSS.0000000000003901 PMCID: PMC7618900 PMID: 41843412 [Indexed for MEDLINE] Conflict of interest statement: Conflict of interest SG received research funding from Kappa Bioscience AS, a company that manufactures and sells vitamin K2. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus.

2. Nutrients. 2026 Jan 14;18(2):269. doi: 10.3390/nu18020269. The Differential Effects of Vitamin K Across Glycaemic Outcomes in Prediabetes and Type 2 Diabetes Mellitus. Ahmed SR(1), Mokgalaboni K(1), Phoswa WN(1). Author information: (1)Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida Campus, Roodepoort 1710, South Africa. Background: Vitamin K has emerged as a promising regulator of glucose metabolism in preclinical studies. There is, however, scant evidence to support this promising potential in a clinical setting. Aim: The aim of this study was to confirm the effects of vitamin K supplementation on glycaemic parameters such as fasting blood glucose (FBG), fasting insulin (FI), glycated haemoglobin (HbA1c), insulin resistance (HOMA-IR), and homeostatic model of beta cell function (HOMA-β) across randomised controlled trials (RCTs). Materials and Methods: This meta-analysis used evidence from PubMed, Scopus, and manual screening. Only RCTs were considered for this meta-analysis of interventional studies. The Meta online tool was used to analyse data, with the results reported as either the mean or the standardised mean difference (SMD), alongside 95% confidence intervals (CI). Results: Only eight RCTs were found relevant and analysed; the age of those in the vitamin K group was 50.58 ± 6.91 years, and in the control group, it was 48.19 ± 5.41. The evidence showed a significant reduction in FBG, SMD = -0.22 (-0.39 to -0.05), HbA1c, MD = -1.00%, 95% CI (-1.92 to -0.07), and HOMA-IR, MD = -0.63, 95% CI (-1.20 to -0.06). However, no effect was observed on insulin (SMD = -0.39, 95% CI: -0.91 to 0.13, p = 0.15) and HOMA-β (MD = 6.56, 95% CI (-3.89 to 17.01), p = 0.2184. Low doses of vitamin K2 and vitamin K1 were associated with reduced HbA1c and HOMA-IR, respectively. An intervention of less than 12 weeks was associated with reduced HOMA-IR. Conclusions: This study showed a significant decrease in FBG, HbA1c, and HOMA-IR without affecting insulin or HOMA-β. Nevertheless, the limited number of trials with moderate quality warrants larger, longer-term RCTs with rigorous methodology and direct comparisons of vitamin K isoforms to better assess therapeutic potential. DOI: 10.3390/nu18020269 PMCID: PMC12845305 PMID: 41599883 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest.

Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial.

3. Eur J Nutr. 2025 Dec 19;65(1):9. doi: 10.1007/s00394-025-03814-7. Assessment of vitamin A, vitamin B(2), vitamin B(12), vitamin K, folate, and choline status following 4 months of multinutrient supplementation in healthy vegans: a randomised, double-blind, placebo-controlled trial. Zerback T(1), Koeder C(2)(3), Weder S(1), Sputtek A(4), Eckert GP(5), Keller M(1). Author information: (1)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. (2)Institute for Prevention and Cancer Epidemiology (IPE), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110, Freiburg im Breisgau, Germany. christiankoeder@gmail.com. (3)Research Institute for Plant-Based Nutrition, 35444, Biebertal, Germany. christiankoeder@gmail.com. (4)MVZ Medical Laboratory Bremen GmbH, 28359, Bremen, Germany. (5)Institute of Nutritional Sciences, Justus-Liebig University, 35392, Giessen, Germany. PURPOSE: The aim of the MultiVeg study, a double-blind, randomised controlled trial (RCT), was to investigate the nutritional status of healthy vegans following 4 months of multinutrient supplementation. METHODS: A double-blind, RCT was conducted with 72 vegan adults (19-57 years) in Germany. Data on anthropometric parameters, dietary nutrient intake, and nutritional status were collected. The nutritional status of the participants was assessed at baseline and after 4 months. The results were compared between groups using ANCOVA. The results for vitamins and choline are presented here. RESULTS: After adjustment for baseline values, age, sex, and multiple testing, no significant between-group differences in biomarker concentration changes from baseline to 4 months were observed for vitamin A, retinol-binding protein, transthyretin, beta-carotene, methylmalonic acid, homocysteine, choline, total osteocalcin, carboxylated and undercarboxylated osteocalcin, and folate. In contrast, significant between-group differences in changes were observed for flavin adenine dinucleotide (FAD), serum vitamin B12, holotranscobalamin, and the combined vitamin B12 status indicator (cB12) after adjustment. CONCLUSION: A multinutrient supplement containing 82 µg of vitamin B12 per day significantly positively affected vitamin B12 blood biomarkers in healthy vegans. REGISTRATION: This study was registered in the German Clinical Trials Register (DRKS00028151). © 2025. The Author(s). DOI: 10.1007/s00394-025-03814-7 PMCID: PMC12717231 PMID: 41417236 [Indexed for MEDLINE] Conflict of interest statement: Declarations. Conflict of interest: T.Z., S.W., C.K., A.S., and G.P.E. declare no conflict of interest. M.K. is the managing director of the Research Institute of Plant-Based Nutrition (IFPE) which received funding from Watson Nutrition for conducting the study. Ethical approval: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethics committee of the Faculty of Medicine of the University of Giessen (57/22). Consent to participate: Written consent was obtained from all subjects involved in the study.

The effect of vitamin K2 supplementation on bone turnover biochemical markers in postmenopausal osteoporosis patients: a systematic review and meta-analysis.

4. Front Endocrinol (Lausanne). 2025 Nov 5;16:1703116. doi: 10.3389/fendo.2025.1703116. eCollection 2025. The effect of vitamin K2 supplementation on bone turnover biochemical markers in postmenopausal osteoporosis patients: a systematic review and meta-analysis. Zhang Z(1), Li Y(1), Li J(1), Yuan Y(2), Liu K(2), Shi X(2). Author information: (1)The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China. (2)The Second Affiliated Hospital of Zhejiang Chinese Medical University (Xinhua Hospital of Zhejiang Province), Hangzhou, China. BACKGROUND: Osteoporosis is a metabolic bone disease characterized by decreased bone mass and increased fracture risk. Bone turnover markers, such as osteocalcin (OC), undercarboxylated osteocalcin (ucOC), and other biochemical indicators, are important for assessing bone metabolism. Vitamin K2 influences bone metabolism by enhancing osteocalcin γ-carboxylation. METHODS: This study followed PRISMA guidelines and included randomized controlled trials on the effects of vitamin K2 supplementation on bone turnover biomarkers in postmenopausal osteoporosis patients. Key outcomes included changes in OC, ucOC, and other bone metabolism markers. RESULTS: Nine studies with 2,570 participants were included. Vitamin K2 (VK2) increased osteocalcin (OC; MD 1.86, 95% CI 1.17-2.56) and bone-specific alkaline phosphatase (BAP; MD 1.49, 95% CI 0.98-2.00). It reduced undercarboxylated OC (ucOC; WMD -1.54, 95% CI -2.44 to -0.64) and tartrate-resistant acid phosphatase (TRAP; MD -0.83, 95% CI -1.21 to -0.46). C-terminal telopeptide (CTX) showed a small, statistically significant reduction (MD -0.09, 95% CI -0.14 to -0.05) with uncertain clinical relevance. N-telopeptide (NTX) showed no significant change. CONCLUSIONS: Vitamin K2 supplementation improves key bone turnover biomarkers, particularly OC and ucOC. These findings support its role in bone metabolism, though further long-term studies are needed to confirm clinical benefits, such as increased bone mineral density. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251087067, identifier CRD420251087067. Copyright © 2025 Zhang, Li, Li, Yuan, Liu and Shi. DOI: 10.3389/fendo.2025.1703116 PMCID: PMC12626859 PMID: 41268154 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial.

5. Atherosclerosis. 2025 Nov;410:120540. doi: 10.1016/j.atherosclerosis.2025.120540. Epub 2025 Oct 12. Effects of vitamin K2 and D3 supplementation on epicardial adipose tissue and systemic inflammation: A substudy of the AVADEC trial. Hasific S(1), Ravn EJ(2), Rasmussen LM(3), Mejldal A(4), Dey D(5), Frandsen NE(2), Lindholt JS(6), Auscher S(7), Lambrechtsen J(7), Hosbond S(8), Alan D(8), Urbonaviciene G(9), Becker S(9), Øvrehus KA(2), Diederichsen A(2). Author information: (1)University Hospital, Department of Cardiology, Odense, Denmark. Electronic address: selmahasific@outlook.com. (2)University Hospital, Department of Cardiology, Odense, Denmark. (3)Odense University Hospital, Department of Clinical Biochemistry, Odense, Denmark. (4)OPEN - Open Patient data Explorative Network, Odense University Hospital, Denmark. (5)Cedars-Sinai Medical Center, Biomedical Imaging Research Institute, Los Angeles, United States of America. (6)Odense University Hospital, Department of Cardiothoracic and Vascular Surgery, Odense, Denmark. (7)OUH Svendborg Hospital, Department of Cardiology, Svendborg, Denmark. (8)Lillebaelt Hospital, Department of Cardiology, Vejle, Denmark. (9)Aarhus University Hospital, Department of Cardiology, Aarhus, Denmark. BACKGROUND AND AIMS: Vitamins K2 and D3 may improve cardiovascular health by modulating inflammation and vascular calcification. Inflammation contributes to atherosclerosis and can be assessed through imaging and systemic biomarkers. This study investigated whether vitamin K2 and D3 supplementation reduces inflammation in epicardial adipose tissue (EAT), including pericoronary adipose tissue (PCAT), and systemic inflammation in elderly men at cardiovascular risk. METHODS: In the Aortic Valve DECalcification (AVADEC) trial, 388 men aged 65-74 received daily vitamin K2 (720 μg) and D3 (25 μg) or placebo for 24 months. EAT inflammation was assessed using non-contrast CT [EAT volume and attenuation] and contrast-enhanced CT [PCAT attenuation]. Systemic inflammation was evaluated via hs-CRP, IL-6, TNF-α, Fetuin-A, and osteopontin (OPN). Dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), the inactive form of MGP, served as a proxy for vitamin K2 status. RESULTS: After 24 months, EAT volume increased in the placebo group (Δ5.66 cm3,95% CI 1.35; 9.98) and non-significantly in the vitamin group (Δ3.44 cm3, 95% CI -0.44; 7.33), with an intergroup difference of -2.22 cm3 (95% CI -8.01; 3.57). EAT attenuation declined similarly (intergroup difference: 0.32 HU, 95% CI -0.23; 0.87). PCAT attenuation remained unchanged. No significant changes were seen in systemic markers, though OPN increased modestly in the vitamin group (Δ25.72 pg/mL, 95% CI 2.40; 49.05). dp-ucMGP decreased significantly with supplementation (intergroup difference: 255.31 pmol/L, 95% CI -289.56; -221.05). CONCLUSIONS: Despite reduction in dp-ucMGP, high-dose vitamin K2 and D3 supplementation did not affect EAT, PCAT or systemic inflammation over 24 months. Alternative strategies may be needed to target inflammatory pathways in cardiovascular disease prevention. Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.atherosclerosis.2025.120540 PMID: 41100911 [Indexed for MEDLINE] Conflict of interest statement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Comparison of cheese with and without Propionibacterium freudenreichii subsp. shermanii LMGT 2951 on off-season muscle strength and VO(2) max development in Nordic skiers: a randomized clinical trial.

6. J Int Soc Sports Nutr. 2025 Dec;22(1):2566373. doi: 10.1080/15502783.2025.2566373. Epub 2025 Sep 30. Comparison of cheese with and without Propionibacterium freudenreichii subsp. shermanii LMGT 2951 on off-season muscle strength and VO(2) max development in Nordic skiers: a randomized clinical trial. Lundberg HE(1)(2), Larsen S(2), Mathisen TF(3), Sundgot-Borgen J(1). Author information: (1)Norwegian School of Sports Sciences, Department of Sports Medicine, Oslo, Norway. (2)Meddoc AS, Hvamstubben 14, Skjetten, Norway. (3)Østfold University College, Department of Health and Welfare, Halden, Norway. BACKGROUND AND OBJECTIVE: Nordic skiers represent a low-impact, weight-sensitive sport and may be inclined to engage in weight-controlling behavior, hence increasing their risk for low energy availability and impairment in health and performance. Jarlsberg cheese (J) is rich in vitamin K₂ from fermentation by Propionibacterium freudenreichii subsp. shermanii LMGT 2951 (Pf) and lactic acid bacteria and increases the osteocalcin (OC) level. Vitamin K is essential for activating OC, which is described to be associated positively with muscle strength, whereas propionic acid bacteria are found to enhance endurance. Except for Pf and its by-products, J and Norvegia (N) cheeses have almost identical nutrient content. The objective of this study was to compare the effects of Jarlsberg and N as potential supplements to training on muscle strength (MS), lean body mass (LBM) and VO2 max. METHODS: Thirty female and 30 male Nordic skiers were block randomized 1:1 to either J or N and studied during a 24-week offseason training schedule. The Norvegia group served as a control group. Females and males were treated with 75 and 90 grams/day, respectively. MS by seated pulldown and half-squat, LBM by DXA, and VO2 max were measured at baseline and after the 24 weeks off-season period. Dietary intake and training hours were registered and monitored at baseline and every eight weeks during the study. RESULTS: MS significantly increased in both groups after 24 weeks (p < 0.01). The mean increase difference in MS-upper body favored Jarlsberg by 0.95 kg (95% CI: -0.02-1.46), approaching significance (p = 0.06). No significant difference was found between groups in MS-lower body. LBM and VO2-max both increased significantly in each group (p ≤ 0.05), with no notable differences between groups. Correlation analysis identified LBM as the dominant outcome variable at both baseline and 24 weeks. Endurance training was the dominant input variable and correlated significantly positively both multiply and partially to LBM, (p = 0.04, p = 0.02), respectively. At baseline and 24-weeks sex, endurance training along with OC-level explained 65% and 68% of the LBM variations, respectively. CONCLUSION: Both Jarlsberg cheese, characterized by its unique Propionibacterium freudenreichii content, and Norvegia cheese, when combined with off-season training, led to increases in LBM, VO₂ max, and MS, with no significant differences observed between groups. However, there was a trend toward greater improvements in MS in the Jarlsberg group. Overall, increases in LBM through structured training appear to be a key driver of gains in both muscle strength and aerobic capacity. PROTOCOL NUMBER: XCS-Jarlsberg/IIA. CLINICALTRIAL.GOV: NCT06688032. DOI: 10.1080/15502783.2025.2566373 PMCID: PMC12486453 PMID: 41025612 [Indexed for MEDLINE] Conflict of interest statement: No potential conflict of interest was reported by the author(s).

Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

7. Prostaglandins Other Lipid Mediat. 2025 Mar;177:106970. doi: 10.1016/j.prostaglandins.2025.106970. Epub 2025 Mar 5. Effect of Menaquinone-7 (MK-7) Supplementation on Anthropometric Measurements, Glycemic Indices, and Lipid Profiles: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nikpayam O(1), Jafari A(2), Faghfouri A(3), Pasand M(4), Noura P(4), Najafi M(4), Sohrab G(5). Author information: (1)Department of Nutrition, School of Health, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: nikpayamomid@gmail.com. (2)Student Research Committee, Department of Community Nutrition, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran. (3)Maternal and Childhood Obesity Research Center, Urmia University of Medical Sciences, Urmia, Iran. (4)Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (5)Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: golbonsohrab@yahoo.com. BACKGROUND: Menaquinone-7 (MK-7) is a type of vitamin K that has a longer half-life and stays in the body for a more extended period compared to other types of vitamin K. Recently, the effects of this vitamin on body weight, glycemic control, and lipid profiles have garnered much attention. AIM OF THE REVIEW: This systematic review and meta-analysis were performed to evaluate the effects of MK-7 on anthropometric measurements, glycemic indices, and lipid profiles. METHODS: A systematic search via appropriate keywords was conducted in electronic databases including PubMed, Scopus, Web of Science, and Google Scholar up to October 2023 to obtain relevant original articles. The quality of studies was evaluated using the Cochrane Collaboration tool. Six original articles met our criteria and were included in the analysis. RESULTS: Statistical analysis showed that MK-7 had a desirable effect on inulin (SMD= -0.56; 95 % CI: -0.77, -0.36; P = 0.000, I2 = 84 %, P = 0.000), HbA1c (SMD=-0.32; 95 % CI: -0.55, -0.09; P = 0.007, I2 = 86.8 %, P = 0.000), and homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (SMD= -0.56; 95 % CI: -0.76, -0.35; P = 0.000, I2 = 84.3 %, P = 0.000). Additionally, subgroup analysis revealed negligible effects of MK-7 on total cholesterol (TC), insulin, HbA1c, and HOMA-IR in both genders of patients who received ≤ 90 mg MK-7 for less than 12 weeks. However, MK-7 didn't have any meaningful effect on other factors. CONCLUSION: Based on the findings of the present systematic review and meta-analysis, MK-7 may have beneficial effects on glycemic control and TC, although further highly qualified original research is needed for a consistent conclusion. Copyright © 2025 Elsevier Inc. All rights reserved. DOI: 10.1016/j.prostaglandins.2025.106970 PMID: 40054729 [Indexed for MEDLINE] Conflict of interest statement: Declaration of Competing Interest None

No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study.

8. J Ren Nutr. 2024 Jul;34(4):337-342. doi: 10.1053/j.jrn.2023.11.007. Epub 2023 Dec 19. No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study. Bladbjerg EM(1), Levy-Schousboe K(2), Frimodt-Møller M(3), Kjærgaard KD(4), Strandhave C(5), Brasen CL(6), Frandsen NE(2), Hansen D(7), Marckmann P(8). Author information: (1)Department of Clinical Biochemistry, Unit for Thrombosis Research, Esbjerg Hospital, University Hospital of Southern Denmark, Esbjerg, Denmark; Department of Regional Health Research, University of Southern Denmark, Denmark. Electronic address: ebladbjerg@health.sdu.dk. (2)Department of Medicine, Zealand University Hospital, Roskilde, Denmark. (3)Steno Diabetes Center, Copenhagen, Denmark; Department of Nephrology, Herlev University Hospital, Copenhagen, Denmark. (4)Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. (5)Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark. (6)Department of Biochemistry and Immunology, Lillebælt Hospital, University Hospital of Southern Denmark; Department of Regional Health Research, University of Southern Denmark, Denmark. (7)Department of Nephrology, Herlev University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. (8)Department of Medicine Sønderborg-Tønder, Hospital Sønderjylland, Sønderborg, Denmark. OBJECTIVE: Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. METHODS: Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52 weeks of vitamin K (MK-7, 360 μg/daily, n = 61) or placebo (n = 62). Measurements at baseline and after 52 weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1 + 2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52 weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. RESULTS: A between-group difference at 52 weeks was observed for PIVKA-II (P < .001). PIVKA-II decreased significantly from baseline to 52 weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P = .04), and no between-group differences in adverse events and serious adverse events. CONCLUSION: One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment. Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. DOI: 10.1053/j.jrn.2023.11.007 PMID: 38128853 [Indexed for MEDLINE]

The effect of six-month oral vitamin K supplementation on calcification propensity time in individuals with type 2 diabetes mellitus: A post hoc analysis of a randomized, double-blind, placebo-controlled trial.

9. Atherosclerosis. 2024 Jul;394:117307. doi: 10.1016/j.atherosclerosis.2023.117307. Epub 2023 Oct 6. The effect of six-month oral vitamin K supplementation on calcification propensity time in individuals with type 2 diabetes mellitus: A post hoc analysis of a randomized, double-blind, placebo-controlled trial. Meer R(1), Romero Prats ML(2), Vervloet MG(3), van der Schouw YT(4), de Jong PA(5), Beulens JWJ(6). Author information: (1)Department of Epidemiology & Data Science, Amsterdam UMC - Location Vrije Universiteit, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, the Netherlands. Electronic address: r.meer@amsterdamumc.nl. (2)Department of Epidemiology & Data Science, Amsterdam UMC - Location Vrije Universiteit, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, the Netherlands. (3)Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, the Netherlands; Department of Nephrology, Amsterdam UMC - Location VUmc, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands. (4)Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands. (5)Department of Radiology, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands. (6)Department of Epidemiology & Data Science, Amsterdam UMC - Location Vrije Universiteit, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam, the Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, the Netherlands; Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. BACKGROUND AND AIMS: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). METHODS: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 μg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F-Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. RESULTS: Median baseline T50 was similar in the vitamin K (350 [321-394] minutes) and placebo groups (363 [320-398]). There was no significant difference in T50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94-1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were -0.185 (p = 0.156) and -0.121 (p = 0.358), respectively. CONCLUSIONS: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted. Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved. DOI: 10.1016/j.atherosclerosis.2023.117307 PMID: 37852868 [Indexed for MEDLINE]

Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial.

10. BMJ Open. 2023 Sep 22;13(9):e073761. doi: 10.1136/bmjopen-2023-073761. Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial. Seely D(1)(2)(3), Legacy M(4)(2), Conte E(4), Keates C(4), Psihogios A(4), Ramsay T(2)(5), Fergusson DA(2)(5), Kanji S(2)(6), Simmons JG(2)(7), Wilson K(2)(7)(8). Author information: (1)Patterson Institute for Integrative Oncology Research, Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada dseely@thechi.ca. (2)Ottawa Hospital Research Institute, Ottawa, Ontario, Canada. (3)School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada. (4)Patterson Institute for Integrative Oncology Research, Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada. (5)School of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada. (6)Department of Pharmacy, Ottawa Hospital, Ottawa, Ontario, Canada. (7)Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. (8)Bruyère Research Institute, Ottawa, Ontario, Canada. BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 μg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2023-073761 PMCID: PMC10533655 PMID: 37739466 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: None declared.

Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial.

11. BMJ Open. 2023 Jul 14;13(7):e073233. doi: 10.1136/bmjopen-2023-073233. Effects of vitamins K2 and D3 supplementation in patients with severe coronary artery calcification: a study protocol for a randomised controlled trial. Hasific S(1), Øvrehus KA(1), Hosbond S(2), Lambrechtsen J(3), Kumarathurai P(1), Mejldal A(4)(5), Ravn EJ(1), Rasmussen LM(6)(7), Gerke O(8), Mickley H(1), Diederichsen A(9). Author information: (1)Department of Cardiology, Odense University Hospital, Odense, Denmark. (2)Department of Cardiology, Sygehus Lillebalt, Vejle, Syddanmark, Denmark. (3)Department of Cardiology, Svendborg Hospital, Svendborg, Denmark. (4)Department of Clinical Research, University of Southern Denmark, Odense, Denmark. (5)Open Patient Data Explorative Network, Odense University, Odense, Denmark. (6)Department of Clinical Biochemistry and Pharmacology, Odense Universitetshospital, Odense, Denmark. (7)Centre for Individualised Medicine in Arterial Diseases, Odense Universitetshospital, Odense, Denmark. (8)Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. (9)Department of Cardiology, Odense University Hospital, Odense, Denmark axel.diederichsen@rsyd.dk. INTRODUCTION: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process. METHOD AND ANALYSIS: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses. ETHICS AND DISSEMINATION: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported. TRIAL REGISTRATION NUMBER: NCT05500443. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2023-073233 PMCID: PMC10351276 PMID: 37451735 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: None declared.

The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial.

12. Arch Osteoporos. 2023 Jun 20;18(1):83. doi: 10.1007/s11657-023-01288-w. The additive effect of vitamin K supplementation and bisphosphonate on fracture risk in post-menopausal osteoporosis: a randomised placebo controlled trial. Moore AE(1), Dulnoan D(1), Voong K(2), Ayis S(3), Mangelis A(3), Gorska R(2), Harrington DJ(2), Tang JCY(4)(5), Fraser WD(4)(5), Hampson G(6)(7)(8). Author information: (1)Osteoporosis Unit, Guy's Hospital, London, UK. (2)Nutristasis Unit, Synnovis Analytics, St Thomas' Hospital, London, UK. (3)School of Life Course and Population Sciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London, UK. (4)Norwich Medical School, University of East Anglia, Norwich, UK. (5)Depts of Endocrinology and Clinical Biochemistry Norfolk and Norwich University Hospitals Trust, Norwich, UK. (6)Osteoporosis Unit, Guy's Hospital, London, UK. geeta.hampson@kcl.ac.uk. (7)Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK. geeta.hampson@kcl.ac.uk. (8)Metabolic Bone Clinic, Department of Diabetes and Endocrinology, St Thomas' Hospital, London, UK. geeta.hampson@kcl.ac.uk. This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. PURPOSE: Some clinical studies have suggested that vitamin K prevents bone loss and may improve fracture risk. The aim was to assess whether vitamin K supplementation has an additive effect on bone mineral density (BMD), hip geometry and bone turnover markers (BTMs) in post-menopausal women with osteoporosis (PMO) and sub-optimum vitamin K status receiving bisphosphonate, calcium and/or vitamin D treatment. METHODS: We conducted a trial in 105 women aged 68.7[12.3] years with PMO and serum vitamin K1 ≤ 0.4 µg/L. They were randomised to 3 treatment arms; vitamin K1 (1 mg/day) arm, vitamin K2 arm (MK-4; 45 mg/day) or placebo for 18 months. They were on oral bisphosphonate and calcium and/or vitamin D. We measured BMD by DXA, hip geometry parameters using hip structural analysis (HSA) software and BTMs. Vitamin K1 or MK-4 supplementation was each compared to placebo. Intention to treat (ITT) and per protocol (PP) analyses were performed. RESULTS: Changes in BMD at the total hip, femoral neck and lumbar spine and BTMs; CTX and P1NP did not differ significantly following either K1 or MK-4 supplementation compared to placebo. Following PP analysis and correction for covariates, there were significant differences in some of the HSA parameters at the intertrochanter (IT) and femoral shaft (FS): IT endocortical diameter (ED) (% change placebo:1.5 [4.1], K1 arm: -1.02 [5.07], p = 0.04), FS subperiosteal/outer diameter (OD) (placebo: 1.78 [5.3], K1 arm: 0.46 [2.23] p = 0.04), FS cross sectional area (CSA) (placebo:1.47 [4.09],K1 arm: -1.02[5.07], p = 0.03). CONCLUSION: The addition of vitamin K1 to oral bisphosphonate with calcium and/or vitamin D treatment in PMO has a modest effect on parameters of hip geometry. Further confirmatory studies are needed. TRIAL REGISTRATION: The study was registered at Clinicaltrial.gov:NCT01232647. © 2023. The Author(s). DOI: 10.1007/s11657-023-01288-w PMCID: PMC10282078 PMID: 37338608 [Indexed for MEDLINE] Conflict of interest statement: "Amelia Moore, Dwight Dulnoan, Kieran Voong, Salma Ayis, Anastasios Mangelis, Renata Gorska, Dominic. J. Harrington and Jonathan CY Tang declare that they have no conflict of interests’. William D. Fraser has received past educational grants, speaker honoraria and been on advisory boards in relation to Vitamin D and all treatments for osteoporosis. Geeta Hampson has received speaker honoraria and been on advisory boards in relation to Vitamin D and all treatments for osteoporosis.

Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial.

13. Nutrients. 2023 May 23;15(11):2422. doi: 10.3390/nu15112422. Effect of Menaquinone-7 Supplementation on Arterial Stiffness in Chronic Hemodialysis Patients: A Multicenter Randomized Controlled Trial. Naiyarakseree N(1), Phannajit J(1)(2)(3), Naiyarakseree W(4), Mahatanan N(1), Asavapujanamanee P(5), Lekhyananda S(6), Vanichakarn S(6), Avihingsanon Y(1), Praditpornsilpa K(1), Eiam-Ong S(1), Susantitaphong P(1)(2). Author information: (1)Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. (2)Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. (3)Division of Clinical Epidemiology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. (4)Division of Nephrology, Department of Medicine, Bangkok Christian Hospital, Bangkok 10500, Thailand. (5)Hemodialysis Center BENCHAKITTI-MDCU, Benjakitti Park Hospital, Bangkok 10330, Thailand. (6)The Kidney Foundation of Thailand, Bangkok 10700, Thailand. BACKGROUND: There is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients. METHODS: This open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome. RESULTS: Baseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks. CONCLUSION: Vitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation. DOI: 10.3390/nu15112422 PMCID: PMC10255064 PMID: 37299386 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflict of interest. The sponsors had no role in the design, execution, interpretation, or writing of the study.

Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health.

14. BMJ Open. 2023 May 19;13(5):e071885. doi: 10.1136/bmjopen-2023-071885. Study protocol of the InterVitaminK trial: a Danish population-based randomised double-blinded placebo-controlled trial of the effects of vitamin K (menaquinone-7) supplementation on cardiovascular, metabolic and bone health. Kampmann FB(1), Thysen SM(1), Nielsen CFB(1), Kofoed KF(2)(3), Køber L(2), Pham MHC(2), Vaag A(4)(5)(6), Jørgensen NR(3)(7), Petersen J(1)(8), Jacobsen RK(1), Kårhus LL(1), Diederichsen A(9)(10), Frimodt-Møller M(4), Linneberg A(11)(3). Author information: (1)Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. (2)Department of Cardiology and Radiology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. (3)Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark. (4)Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark. (5)Department of Clinical Sciences, Lund University Diabetes Center, Malmö, Sweden. (6)Department of Endocrinology, Skåne University Hospital, Malmö, Sweden. (7)Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. (8)Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. (9)Department of Cardiology, Odense University Hospital, Odense, Denmark. (10)Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark. (11)Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark allan.linneberg@regionh.dk. INTRODUCTION: Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification. METHODS AND ANALYSIS: The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance. ETHICS AND DISSEMINATION: Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported. TRIAL REGISTRATION NUMBER: NCT05259046. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. DOI: 10.1136/bmjopen-2023-071885 PMCID: PMC10201225 PMID: 37208133 [Indexed for MEDLINE] Conflict of interest statement: Competing interests: FBK, SMT and AL have received funds and tablets for the trial from Kappa Bioscience AS. AL discloses the application of a patent on vitamin K on lung function for prognostic and therapeutic purposes. Aside from this, the authors declare no conflicts of interest.